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1
Radiation & Cataract: A New Challenge
Madan Rehani, PhD Radiation Protection of Patients Unit, IAEA, Vienna, Austria
Lawrence Dauer, PhDMedical Physics, Memorial Sloan-Kettering Cancer Center
What is cataract?
Clouding or opacification of the natural lens of the
eye and obstructing the passage of light
Rehani & Dauer AAPM/COMP 2011 2
Cataract
Lenticular Opacification
Risk Factors:
Corticosteroids
Diabetes Mellitus
Sunlight exposure (UVB)
Trauma
Infections
Nutritional deprivation
Age (~ 50% >65 yrs)
Heredity
Radiation
Rehani & Dauer AAPM/COMP 2011 4Rehani & Dauer AAPM/COMP 2011
2
What is treatment?
Easily treatable condition -surgery
Nothing to match naturalRehani & Dauer AAPM/COMP 2011 5
Phacoemulsification
• Eye's internal lens is emulsified with an
ultrasonic handpiece
• Aspirated from the eye.
• Aspirated fluids replaced with irrigation of
balanced salt solution
Rehani & Dauer AAPM/COMP 2011 6
Rehani & Dauer AAPM/COMP 2011 7
Dot Opacities
Latency depends on rate at
which damaged epithelial
cells undergo fibrogenesis
and accumulate.
Radiation & Cataract
HOT Topic in Occupational Radiation
Protection
Rehani & Dauer AAPM/COMP 2011
3
Unlike Patients where……..
Rehani & Dauer AAPM/COMP 2011 9 Rehani & Dauer AAPM/COMP 2011 10
nucleus
CapsuleEpithelium
Capsule
Epithelium
Capsule
Epithelium
Capsule
Epithelium
LENS
PSC
Cataract
CORNEA
a. b.
ANTERIOR
CHAMBER
Capsule
Epithelium
Capsule
Epithelium
Capsule
Epithelium
LENS
PSC
Cataract
CORNEA
a. b.
ANTERIOR
CHAMBER
4
• Cortical
• Nuclear
• Posterior SubCapsular (psc)
• Mixed
Major Cataract Subtypes
Rehani & Dauer AAPM/COMP 2011 13 14Rehani & Dauer AAPM/COMP 2011
History of radiation cataract
• Documented within 1 year of Roentgen’s
discovery of X rays
• H. Chalupecky, Ueber die wirkung der
Roentgenstrahlen. Centralblatt fuer
praktische Augenheilkunde (J. Hirschberg
Ed.), pp. 386–401. Veit, Leipzig, 1897.
Rehani & Dauer AAPM/COMP 2011 15
History of radiation cataract-II
• However, cataract was long thought to result
from only high doses of radiation to the lens of
the eye.
• This was based on data from early cyclotron
workers with cataract after substantial
neutron doses and
• with early Japanese A-bomb studies that
reported excess cataracts among those who
received over 2–3 Gy.
Rehani & Dauer AAPM/COMP 2011 16
5
Up to early 1950’s
• W. Rohrschneider, Beitrag zur entstehung und morphologie der ro¨ntgenstrahlenkatarakt. Klin. Monatsbl. Augenheilkd. 81, 254–259 (1928).
• A. U. Desjardins, Action of Roentgen rays and radium on the eye and ear. Am. J. Roentgenol. 26, 643–679 (1931).
• P. J. Leinfelder and H. D. Kerr, Roentgen-ray cataract: An experimental, clinical, and microscopic study. Am. J. Ophthalmol. 19, 739–756 (1936).
• D. G. Cogan and K. K. Dreisler, Minimal amount of x-ray exposure causing lens opacities in the human eye. AMA Arch. Ophthalmol. 50, 30–34 (1953).
Rehani & Dauer AAPM/COMP 2011 17 Rehani & Dauer AAPM/COMP 2011 18
• G. R. Merriam and E. Focht, A clinical study of
radiation cataracts and the relationship to dose.
Am. J. Roentgenol. Radium Ther. Nucl. Med. 77,
759–785 (1957).
• G. R. Merriam and E. F. Focht, A clinical and
experimental study of the effect of single and
divided doses of radiation on cataract
production. Trans. Am. Ophthalmol. Soc. 60, 35–
52 (1962).
Rehani & Dauer AAPM/COMP 2011 19
Beliefs based on data in late 1950’s
• Cataract has a dose threshold
• The severity increased and the latency decreased
as the radiation dose increased above that
threshold
• Latent period was strongly inversely correlated
with dose and that there was no cataract
induction below 2 Gy.
Rehani & Dauer AAPM/COMP 2011 20
6
Other major papers that influenced
• M. D. Nefzger, R. J. Miller and T. Fujino, Eye findings in atomic bomb survivors of Hiroshima and Nagasaki: 1963–1964. Am. J.Epidemiol. 89, 129–138 (1969).
• M. Otake and W. Schull, Radiation-related posterior lenticular opacities in Hiroshima and Nagasaki atomic bomb survivors based on the DS86 dosimetry system. Radiat. Res. 121, 3–13 (1990).
Rehani & Dauer AAPM/COMP 2011 21
ICRP 60 and 103
Rehani & Dauer AAPM/COMP 2011 22
…However, new data on the radiosensitivity of the eye with regard to visual impairment are expected.
Rehani & Dauer AAPM/COMP 2011
NCRP
• Visually disabling cataracts of 2–10 Sv
for single brief exposures, and 0.8 Sv for
protracted exposures
Rehani & Dauer AAPM/COMP 2011 24
7
What is New?
Lens opacities being reported at
dose levels below the currently
mentioned threshold in ICRP,
NCRP
Rehani & Dauer AAPM/COMP 2011 25
Odds Ratio
• Is a measure of effect size, describing the
strength of association or non-independence
between two binary data values.
• Odds ratio treats the two variables being
compared symmetrically, and can be estimated
using some types of non-random samples
• Ratio of the odds of an event occurring in one
group to the odds of it occurring in another group
Rehani & Dauer AAPM/COMP 2011 26
27
A-Bomb Survivors
Neriishi et al, Rad Research
168:2007
• Operative Cataract odds
ratio of
~1.4 at 1 Gy
• Dose threshold seen at
0.1 Gy (upper bound of
0.8 Gy).
Rehani & Dauer AAPM/COMP 2011 28
A-Bomb Survivors
Minamoto et al, Int. J Rad Biol
80(5):2004
• Prevalence of cortical and
posterior subcapsular
opacities showed significant
correlation with radiation dose
• Odds ratios of
~1.3 at 1 Gy
Rehani & Dauer AAPM/COMP 2011
8
29
Chernobyl
Worgul et al, Rad Research
167:2007
• Dose effect threshold
< 1 Gy
• UN Chernobyl Forum 2006
• Even low doses of
0.25 Gy may also be
cataractogenic.
Rehani & Dauer AAPM/COMP 2011 30
Airline Pilots
Rafnsson et al, Arch
Ophthalmol. 123:2005
• Cosmic radiation may
be a causative factor in
nuclear cataracts.
• Note – some have
disagreed with this
assertion
Rehani & Dauer AAPM/COMP 2011
31
Aviators / Astronauts
Jones et al, Aviat Space
Environ Med 78:2007
• Military aviators with
cataracts were found to have
a younger average age at
onset compared with
astronauts.
• Prevalence of cataracts was
found to be higher in
astronauts than aviators.
Rehani & Dauer AAPM/COMP 2011 32
Astronauts
Cucinotta
2001 Rehani & Dauer AAPM/COMP 2011
9
33
Astronauts
Cucinotta et al, Rad Research
156:2001
• Relatively low doses of space
radiation are causative of an
increased incidence and early
appearance of cataracts
• Increased risk with higher
lens doses > 8 mSv
Rehani & Dauer AAPM/COMP 2011 34
Infancy Exposures
Hall et al, Rad Research
152:1999
• Children exposed to lenticular
doses during skin hemangioma
treatments 1920-1959
• Odds ratio for developing
posterior subcapsular cataract
1.5 at 1 Gy
• Odds ratio for developing
cortical opacity
1.35 at 1 Gy
Rehani & Dauer AAPM/COMP 2011
35
Chronic Low Dose Exposures
Chen et al, Rad Research 156:2001
• Contaminated buildings in Taiwan
• Minor lenticular changes in lenses of young subjects
Rehani & Dauer AAPM/COMP 2011 36
Interventional Radiologists
Haskal & Worgul,
RSNA News 2004:14
• Radiologists
• 5/59 posterior
subcapsular cataracts
• 22/59 small dot-like
opacities (early signs
of radiation damage)
• 1/59 had undergone
cataract surgery in one
eye
Schueller et al, Radiographics 2006Rehani & Dauer AAPM/COMP 2011
10
• Inspection of the Merriam and Focht papers
shows that the observation periods after
irradiation were mostly quite short (average of 8
years)
• They studied only 20 individuals who had
estimated lens doses under 2 Gy,
Rehani & Dauer AAPM/COMP 2011 37
Strength of newer studies over earlier ones
• Negative aspects of earlier studies:
• short follow-up periods,
• failed to take into account increasing latent periods
with decreasing doses,
• relatively few subjects with doses below a few Gy.
• Positive aspects of newer studies: Long follow-
up, larger numbers, lower doses
Rehani & Dauer AAPM/COMP 2011 38
Why longer follow-up?
• The latent period is dependent on the rate at
which damaged epithelial cells undergo aberrant
differentiation (fibergenesis) and accumulate in
the PSC region of the lens cortex .
Rehani & Dauer AAPM/COMP 2011 39 Rehani & Dauer AAPM/COMP 2011 40
11
Active collaborators
Eliseo Vano Norman Kleiman
Ariel Duran KH Sim Olivera Ciraj
A Minanoto
Raul Ramirez A Nader
Plus a team of local ophthalmologistsRehani & Dauer AAPM/COMP 2011 41
IAEA Cataract
Rehani & Dauer AAPM/COMP 2011 42
Objective
To examine the prevalence of radiation-
associated lens opacities among interventional
cardiologists and technical staff and correlate
with occupational radiation exposure
• Not purely a doismetry or effect study
• Dose and effect
Rehani & Dauer AAPM/COMP 2011 43
Background
• Since we are concerned with determination of effect, we need doses incurred in past, not prospective
• Non-availability of records of measured values from routine individual monitoring
• Non-availability of widely accepted methods for retrospective estimation
Rehani & Dauer AAPM/COMP 2011 44
12
Interventional procedures
• Limited occupational dose data, USA/Canada??
• 20-30% of cardiologists do not use dosimeter
routinely (Vano et al, BJR, 2006, 79:383-388)
• In developing countries 40-90%
• Errors in use of dosimeters:
• Identification
• Interchange
• Use of protective devices??
Rehani & Dauer AAPM/COMP 2011 45
Vano et al, Radiology, 2008:
Rehani & Dauer AAPM/COMP 2011 46
Model Value Unit Source Remark
n/a 59 µSv/proc Tsapaki ate all, PMB, 2004 CA, 5 countries, shoulder
dose
n/a 89 µSv/proc Tsapaki ate all, PMB, 2004 PTCA, 5 countries,
Shoulder dose
Philips Optimus M
200 Poly C
260 mSv/y Vano, et al, BJR, 2006 5000 procedure/y
Philips
Integris HM 300
31 mSv/y Vano, et al, BJR, 2006 5000 procedure/y
Philips
Integrtis N-5000
18 mSv/y Vano, et al, BJR, 2006 5000 procedure/y
Philips
Integrtis Allura
3.5 mSv Kuipers et al, Cardiovas Int
Rad, 2008
4 weeks, TLD above the
apron
Philps
Polydiagnost C2
0.21-0.37 mSv/proc Steffino, et al BJR 1996 Ceiling screen in place
Not available 0.11 mSv/proc Pratt and Shaw, BJR, 1993 Ceiling screen and
Goggles in place
CGR DG 300 0.014 mSv/proc Marshall et al, BJR 1995 Eye dose, lead shield
Siemens
Angioskop D
0.28 mSv/proc Calkins et al, circulations,
1991
Eye, Ceiling screen in place
Philips Alura
10FD/20FD. GE
Advantix, Philips
Intergris 3000/5000,
Siemens Axiom bip A
Table 1 Sv//h Vano et al. Radiology 2008. Dose rate at 1 m. h=1.6 m
for different modes (fluoro.
cine..)
Dose information for various studies (I)
Rehani & Dauer AAPM/COMP 2011 47
Model Value Unit Source Remark
Philips Integris Allura 3.85 mSv/4 weeksKuipers et al, J
Inte Card, 2008
TLD dose above the apron, mean value for 7
radiologists
Average 35 institutions 48 mSv/yNiklason at al,
Radiolgy, 1993972 procedures/y, dose above the apron
Philips Integris 3000, II
GE L-U, II6.55 mSv/month
Williams, BJR,
199746 procedures/month, neck dose
Not available Figure 2.b µGy/minWhitby, et al,
BJR, 2005PTCA
Different types of systems,
average values
0.5 (IC)
0.15 (nurses)mSv/proc
Vano et al, BJR ,
1998Without protective tools
Philips Integris V 3000 Figs 3.4,6,7 µGy/minWhitby, BJR,
2003Diagrams for PA, RAO, LAO projections
Different units Table 3 µ Sv/procVano, et al, BJR,
1998TLD dose, eyes, with and without protective screen
Philips Integris HM 3000Figs 4.5. 7-
11µGy/min
Morrish et al
BJR, 2008
Scatter dose rate for fluoroscopy and acquisition for
different projections
Dose information for various studies (II)
Rehani & Dauer AAPM/COMP 2011 48
13
Remarks
• Reported eye lens doses: • 0.3-11 mGy/study (without use of protective devices)
• 0.011-0.33 mGy/study (with protective devices)
• Multiple dosimetry quantities: air kerma, H*(10), Hp(10), Hp(3)…)
• Inaccuracy in dose assessment for nurses due to large variability of location and multiple tasks performed
Rehani & Dauer AAPM/COMP 2011 49
Our Decision
• Typical doses if protective devices are not used
• 0.5 mGy/procedure for interventional cardiologists
• 0.15 mGy/procedure for and nurse
• This exposure corresponds to a typical procedure
of 10 min of fluoroscopy and 800 cine frames
Rehani & Dauer AAPM/COMP 2011 50
Workload:
•number of procedures per week
•fluoroscopy time
•number of cine series per procedure
•number of frames per series
Radiation dose assessment
Typical doses if protective devices are not used:
•0.5 mGy/procedure for interventional cardiologists
•0.15 mGy/procedure for and nurse
Use of protective devices:
•ceiling suspended screens (factor: 0.1)
•leaded glass eyewear (factor: 0.1)
Angulations (factor: 1.8)
Radial access (factor: 2.0)
Rehani & Dauer AAPM/COMP 2011 51
Materials and methods
• Interventional cardiologists and nurses
• Control group
Rehani & Dauer AAPM/COMP 2011 52
14
Dose related parameters (I)
Parameter Source
Number of years in interventional cardiology form
Model of fluoroscopy system used (in the past/now) form
Use of ceiling suspended screens (in % of time period), S form
Use of goggles (in % of time period), G form
Workload: number of procedures/week form
Fluoroscopy time/procedure form
No of frames/procedure
(no of frames/series and series/ procedure)form
Rehani & Dauer AAPM/COMP 2011 53
Dose related parameters (II)
Parameter Source Value Factor
Attenuation of goggles, A literature 90%
Attenuation of ceiling suspended screen, B literature 90%
Distance from isocenter literature 75 cm ISL
For particular procedure. for different models
of interventional systems at eye level scatter
dose:
• Dose rate [Sv/h]
• Normalized dose rate [Sv/mAs]
• Total dose for typical procedure [Sv/study]
literature;
different
sources to
match the
model of the
system
Angulations
literature:
Vano, 2006
Batsou, 1998
Morrish, 2008
1.8
Radial access
literature:
IAEA, 2004
Vano, 2008
2
100
)1(1
AG
100
)1(1
BS
Rehani & Dauer AAPM/COMP 2011 54
Dose assessment
Scenario Calculation
Information about model of the
unit, workload and typical
procedure parameters are available
•Scattered dose rate
•Correction for distance, use of protective
devices, angulation, radial access
•Dose ate eye level for typical procedure
•Annual dose/dose for the whole period use
of a particular system
Information about model and
workload is available
(procedure parameters are not
available)
•Typical exposure parameters from the
literature for a particular or similar type if
system (10 min fluoroscopy time and 800
cine frames)
•Same a previous
Rehani & Dauer AAPM/COMP 2011 55
Angulation for typical procedure (CA)
Betsou et al.
BJR, 1998
Vano et al.
Radiology, 2008.Average
PROJECTION TIME (%) mSv/h mSv/h
PA 11.50 1.00 0.12
PA CD 0.50 1.00 0.01
PA CR 5.90 1.00 0.06
RAO 7.50 1.00 0.08
RAO CD 15.80 1.00 0.16
RAO CR 4.20 1.00 0.04
LAO 26.30 2.00 0.53
LAO CD 11.90 2.50 0.30
LAO CR 15.10 3.00 0.45
L LAT 1.30 5.00 0.07
100.00 1.8
Rehani & Dauer AAPM/COMP 2011 56
15
Rehani & Dauer AAPM/COMP 2011 57 Rehani & Dauer AAPM/COMP 2011 58
Rehani & Dauer AAPM/COMP 2011 59 Rehani & Dauer AAPM/COMP 2011 60
16
Assessment of lens change
• Dilatated slit lamp
examination
• Merriam-Focht scoring
system
• Scores: 0-3.0
• Scores >2.0 correlate
with visual acuity
Rehani & Dauer AAPM/COMP 2011 6162
Rehani & Dauer AAPM/COMP 2011 62
Rehani & Dauer AAPM/COMP 2011 63
Results
Rehani & Dauer AAPM/COMP 2011 64
17
CCI has the highest impact factor of all journals
focusing on interventional/invasive therapies.
IF≈ 2.5
Rehani & Dauer AAPM/COMP 2011 65
PSC changes (score > 0.5)
Interventional cardiologists:
• Prevalence 52% (29/56. 95%
CI: 35-73)
• Significance (Fisher exact
test): p<0.001
• Relative risk: 5.7 (95% CI:
1.5-22)
Nurses:
• Prevalence 45% (5/11. 95%
CI: 15-100)
• Significance (Fisher exact
test): p<0.05
• Relative risk: 5.0 (95% CI:
1.2-21)
Rehani & Dauer AAPM/COMP 2011 66
Subjects NoAge*
(y)
No of years in
interventional
cardiology
Cumulative dose
to the lens (Gy)*
Interventional
cardiologists56
42 ± 7
(31-64)
9.2 ± 6.9
(1.0-33)
3.7 ± 7.5
(0.02-43)
Nurses 1138 ± 11
(25-53)
6.0 ± 4.6
(1.0-14)
1.8 ± 3.1
(0.01-8.5)
Control group 2244 ± 9
(29-57)n/a n/a
*mean ± standard deviation; values in parentheses are ranges
Subjects and cumulative radiation dose
to the lens of the eye
Rehani & Dauer AAPM/COMP 2011 67
Dose response for posterior lens changes in cardiologists and
nurses and associated odds ratios (OR). relative risk (RR)
and 95% confidence intervals (CI)
Dose (Gy)Number of
subjects
Number of subjects
with posterior lens
changes*
OR 95% CI RR 95% CI
0 (Control) 22 2 (9%) 1.0 n/a 1.0 n/a
<1 31 12 (39%) 6.3 1.2-32 4.3 1.0-17
1<2 11 5 (45%) 8.3 1.3-54 5.0 1.1-22
2-<3 9 5 (55%) 12.5 1.7-89 6.1 1.4-26
≥3 16 12 (75%) 30 4.7-189 8.3 2.1-32
34 (51%) 10.3 2.2-48 5.6 1.4-21
*cataract grade 0.5 or higher in one eyeRehani & Dauer AAPM/COMP 2011 68
18
Number of interventional cardiologists with posterior lens changes graded by
severity of lens changes with associated cumulative doses to the lens of the eye
Score N (%)
Dose (Gy)
mean median min max
0 in both eyes 27 48 1.6 0.94 0.02 7.4
0.5 in one eye 8 14 2.4 1.8 0.04 8.4
0.5 in both eyes 18 32 7.4 1.3 0.02 43
>1 in one eye
(0.5 or more in the other eye)3 5 3 2.8 0.24 4.5
Rehani & Dauer AAPM/COMP 2011 69 Rehani & Dauer AAPM/COMP 2011 70
Rehani & Dauer AAPM/COMP 2011 71
Vano, E., Kleiman, N.J., Duran, A, Rehani MM, D Echeverrie,
M Cabreraf. Radiation cataract risk in interventional
cardiology personnel. Radiat. Res. 174, 490-5 (2010). IF≈3.1
• 116 exposed individuals and 93 similarly aged
non-exposed controls
• Relative risk of psc opacities in IC was 3.2 (38%
compared to 12%; p<0.005).
• 21% of nurses and technicians
• Cumulative median values of lens doses were
estimated at 6.0 Sv for cardiologists and 1.5 Sv
for associated medical personnel.
Rehani & Dauer AAPM/COMP 2011 72
19
Conclusions from IAEA studies
• Threshold value, if any, is much lower that
current guidelines indicate
• Dose-response relationship between
occupational exposure and the prevalence of
radiation-associated posterior lens changes
• There is a need to find better means for eye
lens dosimetry
• First ever report among this group
Rehani & Dauer AAPM/COMP 2011 73
Limitations
• Opacities that had not progressed to cause
significant visual disability
• Preliminary investigation of the dose response
relationship
• A study of a larger cohort is needed
Rehani & Dauer AAPM/COMP 2011 74
• Lens of the eye, threshold in absorbed dose is
now considered to be 0.5 Gy (against 0.5 to 2 for
detectable opacities and 5 for visual impairment) .
• Occupational Exposure Lens of Eye Limit
• 20 mSv in a y (against 150), averaged over
defined periods of 5 y, with no single y exceeding
50 mSv
75Rehani & Dauer AAPM/COMP 2011 76
Shielding & Positioning Use Barrier Shielding for Body and Eye Protection
Be aware of Staff Location
Rehani & Dauer AAPM/COMP 2011
20
77
Shielding & Positioning Eye Shielding Imperative
• Leaded Ceiling Shield 98% reduction.
• Leaded Glasses Shield ~74-91%
• Differences in performance related to operator position, likely representing interplay of design and fit.
• Sports wraparound or side shields important.
Rehani & Dauer AAPM/COMP 2011 78Rehani & Dauer AAPM/COMP 2011
Training & Self-Evaluations
• Operators and Staff should be trained in the
machine operation and radiation protection.
• Free Training Programs:
• IAEA has free training program • http://rpop.iaea.org/RPOP/RPoP/Content/-
AdditionalResources/Training/1_TrainingMaterial/Radiology.htm
• MARTIR (Multimedia and Audiovisual
Radiation Protection Training in Interventional
Radiology)• http://ec.europa.eu/energy/wcm/nuclear/cd_rom_martir_project.zip
• Perform frequent Self-Evaluations / Audits
79Rehani & Dauer AAPM/COMP 2011 80
Mitigation Efforts (Training, Behavior Modification & Shielding)
~45% drop in 3 years
Average IR LDE by Year
0
10
20
30
40
50
60
2003 2004 2005 2006 2007 2008
Years
LD
E (
mS
v)
Lieto and Jackson, 2000.
Dauer, 2008
Rehani & Dauer AAPM/COMP 2011
21
Additional Resources
81
CVIR-JVIR, 2010
Rehani & Dauer AAPM/COMP 2011
Additional Resources
82
• http://rpop.iaea.org = IAEA Radiation Protection of Patients
• http://rpop.iaea.org/RPOP/RPoP/Content/Documents/TrainingRadiolo
gy/Lectures/RPDIR-L16.2_Fluoroscopy_doses_WEB.ppt
Rehani & Dauer AAPM/COMP 2011
Learning Objectives
1. To understand the basic information about
radiation cataractogenesis
2. To understand the efficacy of protective tools
3. To become aware about the most recent changes
in recommendation by the ICRP on reduction in
eye lend dose limit
Rehani & Dauer AAPM/COMP 2011 83
d
IAEA
Rehani & Dauer AAPM/COMP 2011 84
22
Rehani & Dauer AAPM/COMP 2011 85